Loss of Function of Intestinal IL-17 and IL-22 Producing Cells Contributes to Inflammation and Viral Persistence in SIV-Infected Rhesus Macaques

PLoS Pathogens
Emily S RyanM Paiardini

Abstract

In HIV/SIV-infected humans and rhesus macaques (RMs), a severe depletion of intestinal CD4(+) T-cells producing interleukin IL-17 and IL-22 associates with loss of mucosal integrity and chronic immune activation. However, little is known about the function of IL-17 and IL-22 producing cells during lentiviral infections. Here, we longitudinally determined the levels and functions of IL-17, IL-22 and IL-17/IL-22 producing CD4(+) T-cells in blood, lymph node and colorectum of SIV-infected RMs, as well as how they recover during effective ART and are affected by ART interruption. Intestinal IL-17 and IL-22 producing CD4(+) T-cells are polyfunctional in SIV-uninfected RMs, with the large majority of cells producing four or five cytokines. SIV infection induced a severe dysfunction of colorectal IL-17, IL-22 and IL-17/IL-22 producing CD4(+) T-cells, the extent of which associated with the levels of immune activation (HLA-DR(+)CD38(+)), proliferation (Ki-67+) and CD4(+) T-cell counts before and during ART. Additionally, Th17 cell function during ART negatively correlated with residual plasma viremia and levels of sCD163, a soluble marker of inflammation and disease progression. Furthermore, IL-17 and IL-22 producing cell frequency and...Continue Reading

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BETA
PMA
biopsy
biopsies
FACS
PCR

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TreeStar
Prism
FlowJo
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